Dichloromethane → 6-Chloro-4-phenyl-3-(trifluoromethyl)pyridazine

HRID 1485852Notes

Reaction equation

HRID 1485852 reaction equation
[C:1]1([C:7]2[C:12]([C:13]([F:16])([F:15])[F:14])=[N:11][NH:10][C:9](=O)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)([Cl:20])=O.C(=O)([O-])O.[Na+].ClCCl>C(#N)C>[Cl:20][C:9]1[N:10]=[N:11][C:12]([C:13]([F:16])([F:15])[F:14])=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:8]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 24813Phosphorus oxychlorideHCID 516892Sodium Bicarbonate2×HCID 59242657HCID 59242657, compound

Product 1

HCID 592426496-Chloro-4-phenyl-3-(trifluoromethyl)pyridazineYield 12,768.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 5-phenyl-6-trifluoromethyl-2H-pyridazine-3-one (D2) (20.66 g, 0.086 mol) in acetonitrile (150 ml) was added phosphorous oxychloride (20 ml, 0.215 mmol) and the reaction heated at reflux for 1 h. After this period, the reaction mixture was poured into a saturated solution of sodium hydrogen carbonate, ice and dichloromethane. Further solid sodium hydrogen carbonate was then added until gas evolution had ceased. The organic layer was then separated, dried (Na2SO4) and the solvents evaporated in vacuo. The crude residue was then filtered through silica gel, eluting with dichloromethane, in order to remove the minor isomer. After evaporation of the solvent, the crude product was then re-purified by column chromatography (silica; 0-25% ethyl acetate/heptane) to yield D3 (7.1 g, 32%). C11H6ClF3N2 requires 258; Found 259 (MH+).

Workup

  1. temperaturethe reaction heated
  2. temperatureat reflux for 1 h
  3. waitAfter this period
  4. customThe organic layer was then separated
  5. dry with materialdried (Na2SO4)
  6. customthe solvents evaporated in vacuo
  7. filtrationThe crude residue was then filtered through silica gel
  8. washeluting with dichloromethane, in order
  9. customto remove the minor isomer
  10. customAfter evaporation of the solvent
  11. customthe crude product was then re-purified by column chromatography (silica; 0-25% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-144d62539e884a939a31f593804edb8c
Source dataset
uspto-grants-2016_08
Patent number
US09422296B2

Reaction notes

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